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他扎罗汀诱导基因 1 与 Polo 样激酶 2 相互作用,抑制 HCT116 结直肠癌细胞的增殖。

Tazarotene-induced gene 1 interacts with Polo-like kinase 2 and inhibits cell proliferation in HCT116 colorectal cancer cells.

机构信息

Department of Dermatology, Taipei Tzu Chi Hospital, The Buddhist Tzu Chi Medical Foundation, New Taipei, Taiwan.

School of Medicine, Tzu Chi University, Hualien, Taiwan.

出版信息

Cell Biol Int. 2021 Nov;45(11):2347-2356. doi: 10.1002/cbin.11681. Epub 2021 Aug 5.

Abstract

Tazarotene-induced gene 1 (TIG1) is considered to be a tumor suppressor gene that is highly expressed in normal or well-differentiated colon tissues, while downregulation of TIG1 expression occurs in poorly differentiated colorectal cancer (CRC) tissues. However, it is still unclear how TIG1 regulates the tumorigenesis of CRC. Polo-like kinases (Plks) are believed to play an important role in regulating the cell cycle. The performance of PLK2 in CRC is negatively correlated with the differentiation status of CRC tissues. Here, we found that PLK2 can induce the growth of CRC cells and that TIG1 can prevent PLK2 from promoting the proliferation of CRC cells. We also found that the expression of PLK2 in CRC cells was associated with low levels of Fbxw7 protein and increased expression of cyclin E1. When TIG1 was coexpressed with PLK2, the changes in Fbxw7/cyclin E1 levels induced by PLK2 were reversed. In contrast, silencing TIG1 promoted the proliferation of CRC, and when PLK2 was also silenced, the proliferation of CRC cells induced by TIG1 silencing was significantly inhibited. The above research results suggest that TIG1 can regulate the tumorigenesis of CRC by regulating the activity of PLK2.

摘要

Tazarotene 诱导基因 1(TIG1)被认为是一种肿瘤抑制基因,在正常或分化良好的结肠组织中高度表达,而在分化不良的结直肠癌(CRC)组织中 TIG1 表达下调。然而,TIG1 如何调节 CRC 的肿瘤发生仍然不清楚。Polo 样激酶(Plks)被认为在调节细胞周期中发挥重要作用。PLK2 在 CRC 中的表现与 CRC 组织的分化状态呈负相关。在这里,我们发现 PLK2 可以诱导 CRC 细胞的生长,而 TIG1 可以阻止 PLK2 促进 CRC 细胞的增殖。我们还发现,CRC 细胞中 PLK2 的表达与 Fbxw7 蛋白水平降低和 cyclin E1 表达增加有关。当 TIG1 与 PLK2 共表达时,PLK2 诱导的 Fbxw7/cyclin E1 水平的变化被逆转。相反,沉默 TIG1 促进 CRC 的增殖,而当 PLK2 也被沉默时,TIG1 沉默诱导的 CRC 细胞增殖明显受到抑制。上述研究结果表明,TIG1 可以通过调节 PLK2 的活性来调节 CRC 的肿瘤发生。

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